The concentration of interferon-γ and interleukin-17 in the AA group were higher (<i>p</i> = 0.004; <i>p</i> = 0.003), whereas the concentration of <i>TGF-β</i> decreased (<i>p</i> = 0.044).
Interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) have been implicated historically in the immune pathophysiology of aplastic anemia (AA) and other bone marrow (BM) failure syndromes.
The data suggest that AA occurs when IFN-γ inhibits the generation of myeloid progenitors and prevents lineage differentiation, as opposed to infiltration of activated T cells.
Plasma IL-18, IFN-γ and IL-4 levels were measured in patients with newly diagnosed AA (n = 29), AA in remission (n = 22) and healthy subjects (n = 30) via enzyme-linked immunosorbent assay (ELISA).
Eight SNP loci in five cytokine genes, including tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), transforming growth factor-beta (TGF-β), interleukin-6 (IL-6), and IL-10, and aplastic anemia (AA) were assessed.
Our findings suggest that alterations in KIR/KIR-L matching, such as increased 3DL2 and decreased 2DS1 mismatch, and in the polymorphisms of TGFβ1, IFN-γ, TNF- α and IL-10 may account for the propensity to immunemediated killing of hematopoietic stem cells and/or ineffective hematopoiesis characteristic of AA and MDS.
The results showed that the frequency of IFN-γ +874 TT genotype in patients with aplastic anemia was significantly higher than the corresponding frequency in the healthy adults (42.6% vs. 17.6%, χ(2)=13.78, p=0.01).
Blocking the transcription of the IFN-gamma gene with kinase inhibitors might lead to the development of novel therapeutic agents for patients with aplastic anemia and other autoimmune diseases.
Comparison between the IFN-gamma transcriptome in normal CD34 cells and changes previously detected in CD34 cells from AA and PNH patients reveals the presence of many similarities that may reflect molecular signature of in vivo IFN-gamma exposure.
Homozygosis for (12) CA repeats in the first intron of the human IFN-gamma gene is significantly associated with the risk of aplastic anaemia in Caucasian population.
T cells from aplastic anemia (AA) patients secrete IFN-gamma in vitro, activated cytotoxic lymphocytes infiltrate aplastic bone marrow (BM), and IFN-gamma mRNA, not detected in normal BM, is present in BM from most AA patients.
These findings suggest that the increased peripheral B:9-23rPep-specific IFN-γ immunoreactivity reflects decreased functional β-cell mass and greater disease activity of type 1 diabetes.
Similarly, Interferon γ (IFN-γ), and intracellular free Calcium Ion (ifCa2+) levels were increased in T1D MOs than in control MOs, but the difference did not reach a significant level.
Through functional analysis of the encoding genes coexpressed by the three lncRNAs, we found these genes were mainly enriched in type 1 diabetes and autoimmune thyroid disease pathways, whereas in Gene Ontology (GO) function classification, they were also mainly enriched in the immune response, type I interferon signaling pathways, interferon-γ mediated signaling pathways, and so forth.
The messenger RNA (mRNA) levels and contents of interleukin (IL)-10, IL-4, transforming growth factor (TGF)-β, IL-2, IL-17, and IFN-γ in patients with T1D, healthy volunteers, streptozotocin (STZ)-induced T1D rat model, the control rat, and Treg infusion rats were determined by reverse transcription polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively.
Moreover, the ratio of CCR6-CXCR3+ and CCR6+CXCR3- memory Tregs was altered and the frequency of proliferating Ki67-positive and IFN-γ producing memory Tregs was decreased in children with T1D.